Therapeutic Targets Database
BIDD Pharmainformatics Databases


Target Validation Information
Target NameHistamine H1 receptor    
Type of TargetSuccessful target    
Drug Potency against TargetTranilastIC50 = 100000 nM[1]
BepotastineIC50 = 101 nM[2]
DiphenhydramineIC50 = 1460 nM[3]
CinnarizineIC50 = 1870 nM[3]
TrimeprazineIC50 = 19 nM[3]
TerfenadineIC50 = 200 nM/l[4]
LoratadineIC50 = 290 nM[5]
EpinastineIC50 = 30000 nM[6]
PheniramineIC50 = 33.9 nM/L[7]
PromethazineIC50 = 340 nM[3]
ChlorpheniramineIC50 = 36 nM[3]
AntazolineIC50 = 38.4 nM/L[7]
OxatomideIC50 = 4.5 nM[3]
AzelastineIC50 = 4000 nM/L[8]
AzatadineIC50 = 40000 nM[9]
TriprolidineIC50 = 5.74 nM[10]
LoratadineIC50 = 50 nM/l[11]
KetotifenIC50 = 52 nM[3]
CyclizineIC50 = 5420 nM[3]
MepyramineIC50 = 855000 nM[3]
Mepyramine maleateKd = 4.5 nM[12]
EmedastineKi = 1.3 nM[13]
ErgotidineKi = 10 nM[14]
ErgotidineKi = 10 nM[15]
CetirizineKi = 14 nM[5]
LoratadineKi = 170 nM[16]
OlopatadineKi = 31.6 nM[17]
CetirizineKi = 6 nM[18]
CarebastineIC50 = 0.17 nM/ml[19]
SCH-37370IC50 = 100 nM[5]
ATC-0175IC50 = 150 nM[20]
DIMEBOLINIC50 = 158 nM[21]
MDL-105212IC50 = 3 nM[5]
RUPATADINEIC50 = 3.9 nM[5]
KF-A6IC50 = 3600 nM[23]
9-Phenyl-2,3-dihydro-1H-indeno[2,1-c]pyridineIC50 = 53 nM[24]
MDL-28163IC50 = 59 nM[5]
R-dimethindeneKi = 0.4 nM[26]
9-(2-aminoethyl)-9,10-dihydroanthraceneKi = 137 nM[27]
4,4-Diphenylbutan-1-amineKi = 1670 nM[27]
N-hydroxycarbamate derivativeKi = 17.8 nM[28]
9-(2-aminopropyl)-9,10-dihydroanthraceneKi = 175 nM[27]
9-(Aminomethyl)-9,10-dihydroanthraceneKi = 197 nM[27]
3,3-diphenylpropan-1-amineKi = 2758 nM[27]
N-hydroxycarbamate derivativeKi = 3.63 nM[28]
1-(4-p-Tolyl-butyl)-piperidineKi = 3200 nM[29]
N-methyl-4,4-diphenylbutan-1-amineKi = 386 nM[27]
2-(9,10-dihydroanthracen-9-yl)-N-methylethanamineKi = 48 nM[27]
N-hydroxycarbamate derivativeKi = 5.01 nM[28]
N-hydroxycarbamate derivativeKi = 5.89 nM[28]
N,N-dimethyl-2,2-diphenylethanamineKi = 5172 nM[27]
4-(4-butylpiperidin-1-yl)-1-o-tolylbutan-1-oneKi = 610 nM[30]
N-methyl-3,3-diphenylpropan-1-amineKi = 64 nM[27]
diphenyl(piperidin-4-yl)methanolKi = 659 nM[29]
N-hydroxycarbamate derivativeKi = 7.59 nM[28]
N,N-dimethyl-4,4-diphenylbutan-1-amineKi = 70 nM[27]
R-226161Ki = 74 nM[31]
N,N-Dimethyl-3,3-diphenylpropan-1-amineKi = 75 nM[27]
N-hydroxycarbamate derivativeKi = 9.55 nM[28]
Action against Disease ModelAcrivastineConstitutive H1 receptor activity (inverse agonism) as measured by inhibition of basal l uMinescence in COShuH1 cells, IC50: 40 nM[32]
TranilastIC50 on vascular endotheli uM growth factor-induced chemotaxis in h uMan dermal microvascular endothelial cells: 135000nM,[33]
BromodiphenhydramineInhibition of [3H]mepyramine binding in rat brain Ki: 13.0 nM[34]
CarbinoxamineInhibition of [3H]mepyramine binding in rat brain Ki: 2.3 nM[34]
MethdilazineInhibition of [3H]mepyramine binding in rat brain Ki: 2.3 nM[34]
PhenindamineInhibition of [3H]mepyramine binding in rat brain Ki: 20.0 nM[34]
DiphenylpyralineInhibition of [3H]mepyramine binding in rat brain Ki: 3.2 nM[34]
DimethindeneInhibition of [3H]mepyramine binding in rat brain Ki: 8.0 nM[34]
CyproheptadineThe aim of this study is to find a relationship between serotonin (5-HT) and its metabolite 5-hydroxy indol acetic acid (5-HIAA) in hippocampus, frontal neocortex and platelets. Serotonin and 5-HIAA were measured in cultured neurons and compared with those produced by h uMan platelets. The cortical neuronal 5-HIAA/serotonin ratio was 4.7 and for hippocampal neurons it was 3.2. In h uMan platelets, this ratio was 1.35 suggesting that the highest serotonin metabolism occurs in the frontal neocortex followed by the hippocampus and platelets. In the presence of 0.3 microM of p-chlorophenylalanine both cultured neurons and platelets exhibited an approximately 50% decrease in serotonin and 5-HIAA concentration suggesting similarities in the metabolic profile in both preparations. In addition, we found that serotonin by itself does not play any role in platelet aggregation but potentiates this phenomenon in the presence of calci uM ionophore A23187. This synergistic interaction between serotonin (2-5 microM) and A23187 (0.5-2 microM) was inhibited by serotonin receptor blockers [methysergide (IC50 = 18 microM) and cyproheptadine (IC50, 20 microM)] and calci uM channel blockers (verapamil and diltiazem, IC50 = 20 and 40 microM, respectively) that indicate both mechanisms are receptor mediated. Similarly, U73122, an inhibitor of phospholipase C (PLC), blocked the synergistic effect of serotonin and ionophore at an IC50 value of 9.2 microM. Wortmannin, a phosphoinositide 3-kinase (PI 3-K) inhibitor, also blocked the response (IC50 = 2.6 microM) by inhibiting respiratory burst. However, neither genistein, a tyrosine-specific protein kinase inhibitor, nor chelerythrine, a protein kinase C (PKC) inhibitor, affected aggregation. Our results are strongly suggestive of a synergistic interaction between serotonin type-2 and Ca-ionophore via a PLC/Ca signalling pathway.[35]
Mequitazinebinding of [H]mepyramine to guinea pig lung IC50: 1 nM[36]
Doxepinbinding to guinea-pig brain(Cerebral cortex) Ka :1.7x10(10)[37]
Mizolastineinhibited with high affinity the binding of [3H]pyrilamine to histamine H1 receptors in guinea pig cerebellar membranes and sections. IC50: 47 nM/L[11]
Antazoline hydrochlorideinhibiting h uMan platelet aggregation induced by noradrenaline (2 M) IC50: 1770 nM[38]
Ref 1Jpn J Pharmacol. 1988 Jan;46(1):53-60.Mechanism of inhibitory action of tranilast on the release of slow reacting substance of anaphylaxis (SRS-A) in vitro: effect of tranilast on the release of arachidonic acid and its metabolites. To Reference
Ref 2Bepreve? (bepotastine besilate ophthalmic solution) 1.5% ISTA Pharmaceuticals, Inc. FDA Advisory Committee Briefing Document NDA 22-288 To Reference
Ref 3Br J Pharmacol. 1980 Aug;69(4):663-7.Inhibition of histamine release from human lung in vitro by antihistamines and related drugs. To Reference
Ref 4Arzneimittelforschung. 1982;32(9a):1167-70.Absence of an effect of terfenadine on guinea pig brain histamine H1-receptors in vivo determined by receptor binding techniques. To Reference
Ref 5J Med Chem. 2005 Oct 20;48(21):6523-43.Designed multiple ligands. An emerging drug discovery paradigm. To Reference
Ref 6Arzneimittelforschung. 1995 Jan;45(1):36-40.Comparison of anti-allergic activities of the histamine H1 receptor antagonists epinastine, ketotifen and oxatomide in human leukocytes. To Reference
Ref 7Arch Ophthalmol. 1999 May;117(5):643-7.Inhibition of histamine-induced human conjunctival epithelial cell responses by ocular allergy drugs. To Reference
Ref 8J Allergy Clin Immunol. 1989 Apr;83(4):771-6.The interaction of azelastine with human lung histamine H1, beta, and muscarinic receptor-binding sites. To Reference
Ref 9The inhibition by azatadine of the immunological release of leukotrienes and histamine from human lung fragments. European Journal of Pharmacology, Volume 123, Issue 3, 29 April 1986, Pages 463-465 To Reference
Ref 10Invitrogen company website 2009 To Reference
Ref 11Arzneimittelforschung. 1995 May;45(5):551-8.In vivo and in vitro interaction of the novel selective histamine H1 receptor antagonist mizolastine with H1 receptors in the rodent. To Reference
Ref 12Proc Natl Acad Sci U S A. 1978 Dec;75(12):6290-4.Histamine H1 receptors identified in mammalian brain membranes with [3H]mepyramine. To Reference
Ref 13J Ocul Pharmacol. 1994 Winter;10(4):653-64.Emedastine: a potent, high affinity histamine H1-receptor-selective antagonist for ocular use: receptor binding and second messenger studies. To Reference
Ref 14Curr Top Med Chem. 2006;6(13):1365-73.The emerging role of the histamine H4 receptor in anti-inflammatory therapy. To Reference
Ref 15Drug Discov Today. 2009 Aug;14(15-16):745-53. Epub 2009 May 27.Major advances in the development of histamine H4 receptor ligands. To Reference
Ref 16Curr Drug Discov Technol. 2006 Mar;3(1):1-48.Development and validation of an in silico P450 profiler based on pharmacophore models. To Reference
Ref 17J Pharmacol Exp Ther. 1996 Sep;278(3):1252-61.Characterization of the ocular antiallergic and antihistaminic effects of olopatadine (AL-4943A), a novel drug for treating ocular allergic diseases. To Reference
Ref 18Mol Pharmacol. 2002 Feb;61(2):391-9.Binding characteristics of cetirizine and levocetirizine to human H(1) histamine receptors: contribution of Lys(191) and Thr(194). To Reference
Ref 19Inflamm Res. 1998;47 Suppl 1:S36-7.Towards the optimal antihistamine: studies with ebastine. To Reference
Ref 20Bioorg Med Chem Lett. 2009 Nov 1;19(21):6166-71. Epub 2009 Sep 6.Pyrimidine-based antagonists of h-MCH-R1 derived from ATC0175: in vitro profiling and in vivo evaluation. To Reference
Ref 21Bioorg Med Chem Lett. 2010 Jan 1;20(1):78-82. Epub 2009 Nov 14.Synthesis and biological activity of 5-styryl and 5-phenethyl-substituted 2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indoles. To Reference
Ref 22J Med Chem. 1983 Aug;26(8):1116-22.Synthesis and biological properties of thiophene ring analogues of mianserin. To Reference
Ref 23Antimicrob Agents Chemother. 2007 Nov;51(11):4133-40. Epub 2007 Sep 10.Design, synthesis, and evaluation of 10-N-substituted acridones as novel chemosensitizers in Plasmodium falciparum. To Reference
Ref 24Bioorg Med Chem Lett. 2000 Jun 5;10(11):1277-9.Conformationally-restricted ligands for the histamine H1 receptor. To Reference
Ref 25J Med Chem. 2010 Oct 14;53(19):7021-34.Exploring the neuroleptic substituent in octoclothepin: potential ligands for positron emission tomography with subnanomolar affinity for (1)-adrenoceptors. To Reference
Ref 26J Med Chem. 2009 Sep 10;52(17):5307-10.Characterization of novel selective H1-antihistamines for clinical evaluation in the treatment of insomnia. To Reference
Ref 27Bioorg Med Chem. 2009 Sep 15;17(18):6496-504. Epub 2009 Aug 13.Synthesis, structure-affinity relationships, and modeling of AMDA analogs at 5-HT2A and H1 receptors: structural factors contributing to selectivity. To Reference
Ref 28Bioorg Med Chem Lett. 2005 Feb 15;15(4):1083-5.5-Lipoxygenase inhibition by N-hydroxycarbamates in dual-function compounds. To Reference
Ref 29Bioorg Med Chem Lett. 2009 Sep 1;19(17):5043-7. Epub 2009 Aug 5.Structural determinants for histamine H(1) affinity, hERG affinity and QTc prolongation in a series of terfenadine analogs. To Reference
Ref 30J Med Chem. 2010 Sep 9;53(17):6386-97.Discovery of N-{1-[3-(3-oxo-2,3-dihydrobenzo[1,4]oxazin-4-yl)propyl]piperidin-4-yl}-2-phenylacetamide (Lu AE51090): an allosteric muscarinic M1 receptor agonist with unprecedented selectivity and procognitive potential. To Reference
Ref 31Bioorg Med Chem. 2007 Jun 1;15(11):3649-60. Epub 2007 Mar 21.Tricyclic isoxazolines: identification of R226161 as a potential new antidepressant that combines potent serotonin reuptake inhibition and alpha2-adrenoceptor antagonism. To Reference
Ref 32J Pharmacol Exp Ther. 2002 Jul;302(1):328-36.A novel phenylaminotetralin radioligand reveals a subpopulation of histamine H(1) receptors. To Reference
Ref 33Probing Mesocorticolimbic Dopamine Function In Alcohol Dependence Using Dextroamphetamine Behavioural and FMRI Studies. Xavier Laurent Balducci, Pg 18 To Reference
Ref 34Histamine H1 receptors identified in mammalian brain membranes with [3H]mepyramine. Proc. Nati. Acad. Sci. USA. Vol. 75, No. 12, pp. 6290-6294,, December 1978 To Reference
Ref 35Exp Brain Res. 2007 Nov;183(3):411-6.The metabolism of serotonin in neuronal cells in culture and platelets. To Reference
Ref 36Effect of mequitazine a non sedative antihistamine on brain H1 receptors. Life Sciences. Volume 29, Issue 6, 10 August 1981, Pages 547-552 To Reference
Ref 37Br J Pharmacol. 1985 Feb;84(2):417-24.The binding of doxepin to histamine H1-receptors in guinea-pig and rat brain. To Reference
Ref 38J Pharm Pharmacol. 2004 Feb;56(2):213-20.The effects of imidazoline agents on the aggregation of human platelets. To Reference


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